In a single-institution phase II trial reported in the Journal of Clinical Oncology, Jain et al found that chemotherapy-free treatment with the combination of ibrutinib and rituximab produced high overall and complete response rates in patients with previously untreated mantle cell lymphoma aged ≥ 65 years. Atrial fibrillation was observed in a third of patients.
Study Details
The trial enrolled 50 patients at The University of Texas MD Anderson Cancer Center between October 2015 and November 2019. Patients with a Ki67 level of > 50% and blastoid morphology were excluded. Ibrutinib was given at 560 mg once daily in 28-day cycles. Rituximab was given at 375 mg/m2 once weekly for 4 weeks in cycle 1, on day 1 of every cycle starting in cycles 3 to 8, and on day 1 every 2 months for up to 2 years after cycle 8; after 2 years, ibrutinib was given in continuous cycles until disease progression or unacceptable toxicity. None of the patients received stem cell transplantation.
Responses
Median follow-up was 45 months (interquartile range = 24–56 months). In intent-to-treat analysis, objective response was observed in 46 (92%) of 50 patients, with complete response in 34 (68%). Among 48 patients evaluable for response, objective response was observed in 96%, with complete response in 71%. In analysis according to Ki67 percentage, objective response was observed in 37 (97%; complete response in 74%) of 38 patients with a Ki67 level of < 30% and in 9 (75%; complete response in 50%) of 12 with a Ki67 level of ≥ 30% to 50% (P < .001).
KEY POINTS
- Among response-evaluable patients, objective response was observed in 96%, with complete response in 71%.
- Progression-free and overall survival rates at 3 years were 87% and 94%, respectively.
Among 16 responders with baseline samples assessed by bulk RNA sequencing, differential overexpression of CCND1, BIRC3, BANK1, SETBP1, AXIN2, and IL2RA was observed among 7 patients with partial response vs 9 with complete response.
Median progression-free survival and median overall survival were not reached; 3-year rates were 87% (95% confidence interval [CI] = 73%–94%) and 94% (95% CI = 82%–98%), respectively. A trend toward improved progression-free survival among patients with lower Ki67 was observed (hazard ratio = 2.62) but was not statistically significant (P = .190). No difference in overall survival was observed according to Ki67 percentage (P = .356).
Adverse Events
The most common grade 3 or 4 adverse events were atrial fibrillation (22%), fatigue (18%), diarrhea (14%), and myalgia (14%). Grade 3 or 4 hematologic toxicities consisted of neutropenia in 8% of patients, and anemia and thrombocytopenia in 4% each. Four patients developed grade 3 or 4 bleeding while on ibrutinib. Overall, 17 patients (34%) developed atrial fibrillation, which resulted in discontinuation of ibrutinib in 10 participants; of the 17 patients, 9 had no history of atrial fibrillation. No treatment-related deaths were observed.
The investigators concluded, “Ibrutinib/rituximab combination is effective in older patients with mantle cell lymphoma. Baseline evaluation for cardiovascular risks is highly recommended. [A] randomized trial is needed for definitive conclusions.”
Michael L. Wang, MD, of the Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Pharmacyclics LLC and Janssen. For full disclosures of the study authors, visit ascopubs.org.
